Attenuation of collagen-induced arthritis by hyperbaric oxygen therapy through altering immune balance in favor of regulatory T cells.

Hyperbaric oxygen (HBO₂) therapy is currently used for the treatment of chronic wounds, radiation-induced soft tissue necrosis, several oxygen-deficiency conditions and decompression sickness. In addition to the current indications, much empirical and experimental data suggest that HBO₂ therapy may benefit autoimmune diseases by suppressing immunity, but the underlying mechanism is not well understood. Therefore, in the present study, we investigated whether HBO₂ prevents the development of collagen-induced arthritis (CIA) in association with alteration of the immune balance between pro-inflammatory Th17 and anti-inflammatory regulatory T cells (Tregs). Arthritis was induced in DBA/1 mice by intradermal injection of type II collagen. Animals received either no treatment or 90 minutes of HBO₂ (100% oxygen, at 2.0 ATA) daily beginning three days prior to the injection and were monitored for the development of arthritis. Six weeks later, joint tissues and spleens were analyzed for the alteration of immune balance between Th17 and Tregs by immunohistochemistry (IHC) or Western blot. Injection of collagen-induced extensive arthritis and extramedullary hematopoiesis in the spleens. Meanwhile, joint swelling and inflammatory tissue damages as well as extramedullary hematopoiesis were significantly less severe in the mice treated with HBO₂. Both IHC and Western blot showed a decrease of FOXP3 and an increase of pSTAT3 expressions in the joints and spleens of the mice injected with collagen. This suggested that the systemic immune balance was biased toward Th17 cells, which was reversed by HBO₂ therapy. These results suggested acute CIA associated with an immune balance favoring Th17 was attenuated by HBO₂ in parallel with restoration of the immune balance to favor Tregs.
Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission.
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